title: Synthesis, Activity and Metabolic Stability of Non-Ribose Containing Inhibitors of Histone Methyltransferase DOT1L.
abstract: Histone methyltransferase DOT1L is a drug target for MLL leukemia. We report an efficient synthesis of a cyclopentane-containing compound that potently and selectively inhibits DOT1L (Ki= 1.1 nM) as well as H3K79 methylation (IC50~ 200 nM). Importantly, this compound exhibits a high stability in plasma and liver microsomes, suggesting it is a better drug candidate.
authors.affiliation: Department of Pharmacology, Baylor College of Medicine, 1 Baylor Plaza, Houston, Texas 77030, United States. ; Tel: +1 713-798-7415.
authors.forename: Lisheng
authors.initials: L
authors.lastname: Deng
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yao
authors.forename: Cong
authors.initials: C
authors.lastname: Wang
authors.forename: Michele S
authors.initials: MS
authors.lastname: Redell
authors.forename: Shuo
authors.initials: S
authors.lastname: Dong
authors.forename: Yongcheng
authors.initials: Y
authors.lastname: Song